US4151298A - Anthelmintic compositions - Google Patents

Anthelmintic compositions Download PDF

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Publication number
US4151298A
US4151298A US05/867,653 US86765378A US4151298A US 4151298 A US4151298 A US 4151298A US 86765378 A US86765378 A US 86765378A US 4151298 A US4151298 A US 4151298A
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US
United States
Prior art keywords
group
sub
represents hydrogen
halogen
trifluoromethyl
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Expired - Lifetime
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US05/867,653
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English (en)
Inventor
Jozef Drabek
Alfred Meyer
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Novartis Corp
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Ciba Geigy Corp
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles

Definitions

  • the present invention relates to anthelmintic compositions which contain as active component anilinomethylenemalononitrile derivatives and to their use for combating heliminths, especially Fasciola hepatica, in domestic animals and productive livestock.
  • the active compounds have the general formula I ##STR2## wherein R 1 represents hydrogen, C 1 -C 6 alkyl, the propargyl group or the benzyl radical,
  • R 2 represents hydrogen, C 1 -C 4 alkyl, halogen, the trifluoromethyl group, the nitro group or the cyano group,
  • R 3 represents hydrogen, halogen, the trifluoromethyl group or the nitro group
  • R 4 represents hydrogen or halogen
  • R 1 may only be the propargyl group or the benzyl radical if at least one of the symbols R 2 or R 3 represents the trifluoromethyl group.
  • Active compounds distinguished by a particularly outstanding anthelmintic action are those which fall under the following restricted formula Ia ##STR3##
  • WHEREIN R 1 represents hydrogen, C 1 -C 6 alkyl, the propargyl group or the benzyl radical,
  • R 2 and R 3 each independently of the other, represent hydrogen, halogen, methyl, the trifluoromethyl group or the nitro group, and
  • R 4 represents hydrogen or halogen
  • R 1 may only be the propargyl group or the benzyl radical if at least one of the symbols R 2 or R 3 represents the trifluoromethyl group.
  • compounds which may be regarded as especially active against trematoda are those of the following restricted formula Ib ##STR4## wherein R 1 represents hydrogen, C 1 -C 6 alkyl, the propargyl group or the benzyl radical,
  • R 2 and R 3 each independently of the other, represent chlorine, methyl, the trifluoromethyl group or the nitro group, and
  • R 4 represents hydrogen or chlorine
  • R 1 may only be the propargyl group or the benzyl radical if at least one of the symbols R 2 or R 3 represents the trifluoromethyl group.
  • halogen is to be understood as meaning, fluorine, chlorine, bromine and iodine.
  • alkyl radicals can be straight-chain or branched.
  • alkyl radicals are: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-amyl, isoamyl and also the isomers of the hexyl radical.
  • the compounds of the formula I are obtained by methods which are known per se and which are also performed in the publications referred to above. Accordingly, the compounds of the formula I which are both substituted and unsubstituted at the nitrogen atom of the aniline radical can be prepared by reaction of the suitable aniline compounds with ethoxymethylenemalononitrile. In addition, the compounds of the formula I which are substituted at the nitrogen atom of the aniline radical can be obtained by alkylation with dialkyl sulphate.
  • the anilinomethylenemalononitrile derivatives of the formula I are distinguished by good anthelmintic action against nematoda, cestoda and, especially, trematoda. In particular, their action against fasciolida (Fasciola heptatica) is to be highlighted.
  • the active substances are administered in the form of a suspension with a stomach probe to white mice infected with Nematospiroides dubius.
  • the active compounds are administered to each animal once daily on 3 successive days. The animals are then sacrificed on the 8th day after the start of the treatment and dissected.
  • compositions are tolerated by the mice without any symptoms.
  • the active substances are administered in the form of a suspension with a stomach probe to white mice infected with Nippostrongylus brasiliensis. Five animals are used for each test. The active compounds are administered once daily to each group of animals on successive days. The daily dose per animal is 100 mg of active compound/kg of body weight. The animals are then sacrificed on the 4th day after the start of the treatment and dissected. Evaluation is made after dissection of the test animals by comparing the number of parasites remaining in the intestine with an untreated control which had been infected in the same way at the same time.
  • the active substances are administered in the form of a suspension with a stomach probe to white mice which have been artificially infected with Hymenolepis nana. Five animals are used for each test. The active compounds are administered to each group of animals once daily on 3 successive days. The animals are sacrificed on the 4th day after the start of the treatment and dissected. Evaluation is made after dissection of the animals by comparing the number of tape worms present in the intestine with an untreated control which was infected at the same time in the same way.
  • compositions of the present invention are used for combating helminths in domestic animals and productive livestock, such as cattle, sheep, goats, horses, pigs, cats, dogs and poultry. They can be administered to the animals in both individual and repeated doses. Depending on the species of animal, the individual doses are preferably administered in amounts between 0.5 and 100 mg/kg of body weight. A better action is often attained by protracted administration, or it is possible to manage with lower total doses.
  • the active compounds, or mixtures containing them can also be added to feeds and to troughs.
  • the ready-prepared feeds contain the active compounds of the formula I preferably in a concentration of 0.005 to 0.1% by weight.
  • compositions can be administered to the animals perorally or in the form of solutions, emulsions, suspensions (drenches), powders, tablets, boluses and capsules.
  • Conventional solid carriers are used for preparing these formulations, for example kaolin, talc, bentonite, common salt, calcium phosphate, cotton seed flour or liquids which do not react with the active compounds, such as oils and other solvents and diluents which are harmless to the animal organism.
  • the active compounds can also be administered to the animals by subcutaneous injection.
  • suitable carriers are for example hay, production feeds, cereal feeds or protein concentrates.
  • feeds can contain additives, vitamins, antibiotics, chemotherapeutical agents or other pesticides, chiefly bacteriostats, fungistats, coccidiostats or also hormone preparations, substances having anabolic action or other substances which promote growth, enhance the quality of the flesh of slaughter animals, or are otherwise beneficial to the organism. They can also be combined with other anthelmintic agents, whereby their activity spectrum is broadened and adapted to given circumstances.
  • Nematocides for example Absomal, Alcopar, Anthelcide, Ascaridol, Banmith II, Bephenium, Bradosol, Cambendazol, Calorophos, Chlorthion, Coumaphos, Cyanin, Destomycin, Diethylcarbamazin, Dichlorphen, DDVP, 1,4-di-(D-glyconyl)piperazine, Dithiazonin, Dow ET/70 Douco 132, Dymanthin HCl, Egressin, Gainex, Hexachlorophen, hexylresorcinol, Tonit, Levamisol, Meparin, methylene violet, ethyl-1-methyl-tridecylpiperazinium-4-carboxylate, Methyridin, Monopar, Marlene, Weguvon, Nematodin, Nemural, Nidanthel, Parbendazol, Parvex Phenothiazin, piperazine, polymethylenepiperazine, Prome
  • Cestodicides for example Acranil, Arecolin, Atebrin, Bithionol, dithionol oxide, Bunamidin, Cestodin, Cambendazol, dibutyl tin dilaurate, Dichlorophen, dioctyl tin dichloride, dioctyl tin dilaurate, Filixic acid, Hexachlorophen, Nidanthel, Terenol, Yomesan.
  • Cestodicides for example Acranil, Arecolin, Atebrin, Bithionol, dithionol oxide, Bunamidin, Cestodin, Cambendazol, dibutyl tin dilaurate, Dichlorophen, dioctyl tin dichloride, dioctyl tin dilaurate, Filixic acid, Hexachlorophen, Nidanthel, Terenol, Yomesan.
  • the anthelmintic compositions of the present invention are prepared in a manner known per se by homogeneously mixing and/or grinding active compounds of the formula I with suitable carriers, with or without the addition of dispersants or solvents which are inert to the active compounds.
  • the active substances may be processed to the following formulations:
  • granules coated granules, impregnated granules and homogeneous granules
  • water-dispersible active substance concentrates wettable powders
  • the granular size of the carriers is advantageously up to about 0.1 mm and for granules 10.500 ⁇ (0.01-0.5 mm).
  • the active substance concentrations are from 0.5 to 80%, and in the liquid formulations from 0.5 to 15%.
  • mixtures can also contain additives which stabilise the active substance and/or nonionic, anionic and cationic substances which ensure for example an improved wettability (wetting agents) and dispersibility (dispersants).
  • additives which stabilise the active substance and/or nonionic, anionic and cationic substances which ensure for example an improved wettability (wetting agents) and dispersibility (dispersants).
  • the active substance is homogeneously mixed together with the polyoxyethylene tall oil ester-urea mixture and the polyvinyl pyrrolidone with the addition of about 30% of the silicic acid in a planetary mixer.
  • the remainder of the silicic acid and the bolus alba are then added and the mixture is mixed in suitable mixers until homogeneous, and then ground to a particle size of less than 20 ⁇ in a disc mill.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
US05/867,653 1977-01-10 1978-01-06 Anthelmintic compositions Expired - Lifetime US4151298A (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CH266/77 1977-01-10
CH26677 1977-01-10
CH15001/77 1977-12-07
CH1500177 1977-12-07

Publications (1)

Publication Number Publication Date
US4151298A true US4151298A (en) 1979-04-24

Family

ID=25684078

Family Applications (1)

Application Number Title Priority Date Filing Date
US05/867,653 Expired - Lifetime US4151298A (en) 1977-01-10 1978-01-06 Anthelmintic compositions

Country Status (10)

Country Link
US (1) US4151298A (en, 2012)
AU (1) AU3228078A (en, 2012)
DE (1) DE2800740A1 (en, 2012)
DK (1) DK9078A (en, 2012)
FR (1) FR2376661A1 (en, 2012)
IL (1) IL53767A0 (en, 2012)
IT (1) IT7819093A0 (en, 2012)
NL (1) NL7800191A (en, 2012)
NZ (1) NZ186178A (en, 2012)
SE (1) SE7800189L (en, 2012)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU728672B2 (en) * 1996-08-14 2001-01-18 Notox Ltd. Pharmaceutical compositions comprising tyrphostins
US20040224984A1 (en) * 2003-03-03 2004-11-11 Selph Jeffrey L. Methods of treating inflammations and infections with pyridinium salts
US11655237B2 (en) 2020-03-30 2023-05-23 Gilead Sciences, Inc. Solid forms of a Cot inhibitor compound
US11827662B2 (en) 2019-06-14 2023-11-28 Gilead Sciences, Inc. Cot modulators and methods of use thereof
US11845737B2 (en) 2020-04-02 2023-12-19 Gilead Sciences, Inc. Process for preparing a Cot inhibitor compound
US11905299B2 (en) 2015-07-06 2024-02-20 Gilead Sciences, Inc. Cot modulators and methods of use thereof
US12398160B2 (en) 2023-09-28 2025-08-26 Gilead Sciences, Inc. Cot modulators and methods of use thereof

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4153723A (en) * 1977-01-10 1979-05-08 Ciba-Geigy Corporation Anthelmintic agents
GB8422919D0 (en) * 1984-09-11 1984-10-17 May & Baker Ltd Compositions of matter

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3551573A (en) * 1967-11-08 1970-12-29 Monsanto Co Insecticidal composition and method containing anilinomethylene malonitriles
US3702861A (en) * 1970-08-03 1972-11-14 Monsanto Co Preparation of n-alkyl anilinomethylenemalononitriles
US3982015A (en) * 1974-08-14 1976-09-21 Ciba-Geigy Corporation N-propargyl-anilinomethylenemalodinitrile derivatives
US4000314A (en) * 1975-01-16 1976-12-28 Ciba-Geigy Corporation Pesticidal N-(2,2-dicyanovinyl)-N-benzyl-anilines

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3691227A (en) * 1969-12-09 1972-09-12 Monsanto Co Anilinomethylenemalonitriles
GB1441589A (en) * 1972-10-06 1976-07-07 Fisons Ltd Aminomethylenemalonitriles and their use as fungicides

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3551573A (en) * 1967-11-08 1970-12-29 Monsanto Co Insecticidal composition and method containing anilinomethylene malonitriles
US3702861A (en) * 1970-08-03 1972-11-14 Monsanto Co Preparation of n-alkyl anilinomethylenemalononitriles
US3982015A (en) * 1974-08-14 1976-09-21 Ciba-Geigy Corporation N-propargyl-anilinomethylenemalodinitrile derivatives
US4000314A (en) * 1975-01-16 1976-12-28 Ciba-Geigy Corporation Pesticidal N-(2,2-dicyanovinyl)-N-benzyl-anilines

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU728672B2 (en) * 1996-08-14 2001-01-18 Notox Ltd. Pharmaceutical compositions comprising tyrphostins
US7820696B2 (en) 2003-03-03 2010-10-26 Mycosol, Inc. Compounds and methods for controlling fungi, bacteria and insects
US20040235898A1 (en) * 2003-03-03 2004-11-25 Klein Richard B. Compounds and methods for controlling fungi, bacteria and insects
US7220761B2 (en) 2003-03-03 2007-05-22 Mycosol, Inc. Compounds and methods for controlling fungi, bacteria and insects
US20090137639A1 (en) * 2003-03-03 2009-05-28 Klein Richard B Methods for controlling fungi and bacteria
US7547444B1 (en) 2003-03-03 2009-06-16 Mycosol, Inc. Methods for controlling fungi and bacteria
US20040224984A1 (en) * 2003-03-03 2004-11-11 Selph Jeffrey L. Methods of treating inflammations and infections with pyridinium salts
US8124626B2 (en) 2003-03-03 2012-02-28 Mycosol, Inc. Methods of treating inflammations and infections with pyridinium salts
US11905299B2 (en) 2015-07-06 2024-02-20 Gilead Sciences, Inc. Cot modulators and methods of use thereof
US11827662B2 (en) 2019-06-14 2023-11-28 Gilead Sciences, Inc. Cot modulators and methods of use thereof
US11655237B2 (en) 2020-03-30 2023-05-23 Gilead Sciences, Inc. Solid forms of a Cot inhibitor compound
US11845737B2 (en) 2020-04-02 2023-12-19 Gilead Sciences, Inc. Process for preparing a Cot inhibitor compound
US12365666B2 (en) 2020-04-02 2025-07-22 Gilead Sciences, Inc. Process for preparing a Cot inhibitor compound
US12398160B2 (en) 2023-09-28 2025-08-26 Gilead Sciences, Inc. Cot modulators and methods of use thereof

Also Published As

Publication number Publication date
SE7800189L (sv) 1978-07-11
DK9078A (da) 1978-07-11
IL53767A0 (en) 1978-04-30
NZ186178A (en) 1980-08-26
FR2376661B1 (en, 2012) 1980-04-18
AU3228078A (en) 1979-07-19
DE2800740A1 (de) 1978-07-13
NL7800191A (nl) 1978-07-12
IT7819093A0 (it) 1978-01-06
FR2376661A1 (fr) 1978-08-04

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